Serological Evaluation of Onchocerciasis and Lymphatic Filariasis Elimination in the Bakoye and Falémé foci, Mali Housseini Dolo1,6*, Yaya I. Coulibaly1,2, Moussa Sow3, Massitan Dembélé4, Salif S. Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa318/5811165 by guest on 29 April 2020 Doumbia1, Siaka Y. Coulibaly1, Moussa B. Sangare1, Ilo Dicko1, Abdallah A. Diallo1, Lamine Soumaoro1, Michel E. Coulibaly1, Dansine Diarra5, Robert Colebunders6, Thomas B. Nutman7, Martin Walker8*, Maria-Gloria Basáñez9* 1 Lymphatic Filariasis Research Unit, International Center of Excellence in Research, Faculty of Medicine and Odontostomatology, Point G, Bamako, Mali 2 Centre National d’Appui à la lutte contre la Maladie (CNAM), Bamako, Mali 3 Programme National de Lutte contre l’Onchocercose, Bamako, Mali 4 Programme National d’Elimination de la Filariose Lymphatique, Bamako, Mali 5 Faculty of Geography and History, Bamako, Mali 6 Global Health Institute, University of Antwerp, Antwerp, Belgium 7 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 8 Department of Pathobiology and Population Sciences and London Centre for Neglected Tropical Disease Research, Royal Veterinary College, Hatfield, UK 9 Department of Infectious Disease Epidemiology and London Centre for Neglected Tropical Disease Research, MRC Centre for Global Infectious Disease Analysis, Imperial College London, UK * contributed equally to this work. Correspondence to: Dr Housseini Dolo Lymphatic Filariasis Research Unit International Center of Excellence in Research (ICER Mali) © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc- nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact [email protected] 2 Faculté de Médecine et d'Odontostomatologie (FMOS) BP 1805 Bamako Mali Mobile: + 223 76 28 92 39 Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa318/5811165 by guest on 29 April 2020 [email protected] 2 3 Summary: Ov16–Wb123 seroprevalence was measured in children ≤10 year-old to evaluate onchocerciasis and lymphatic filariasis elimination in two co-endemic foci (Bakoye and Falémé) in Mali under long-term ivermectin treatment, which stopped in 2016. These goals seem to have been achieved. Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa318/5811165 by guest on 29 April 2020 3 4 Abstract Background. In Mali, ivermectin-based onchocerciasis elimination from the Bakoye and Falémé foci, reported in 2009–2012, was a beacon leading to policy shifting from morbidity control to elimination of transmission (EOT). These foci are also endemic for lymphatic Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa318/5811165 by guest on 29 April 2020 filariasis (LF). In 2007–2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24–25 years of treatment to evaluate if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved. Methods. The SD Bioline Onchocerciasis/LF IgG4 biplex rapid diagnostic test (RDT) was used in 2,186 children aged 3–10 years in 13 villages (plus two hamlets) in Bakoye, and 2,270 children in 15 villages (plus one hamlet) in Falémé. In Bakoye, all-age serosurveys were conducted in three historically hyperendemic villages, testing 1,867 individuals aged 3– 78 years. Results. In Bakoye, IgG4 seropositivity was 0.27% (95%CI=0.13–0.60%) for both Ov16 and Wb123 antigens. In Falémé, Ov16 and Wb123 seroprevalence was, respectively, 0.04% (95%CI=0.01–0.25%) and 0.09% (95%CI=0.02–0.32%). Ov16-seropositive children were from historically meso- and hyperendemic villages. Ov16 positivity was <2% in those ≤14 years, increasing to 16% in those ≥40 years. Wb123 seropositivity was <2% in those ≤39 years, reaching 3% in those ≥40 years. Conclusions. Notwithstanding uncertainty in the biplex RDT sensitivity, Ov16 and Wb123 seroprevalence among children in Bakoye and Falémé appears consistent with EOT (onchocerciasis) and EPHP (LF) since stopping treatment in 2016. The few Ov16- seropositive children should be skin-snip PCR tested and followed up. Key words: onchocerciasis, lymphatic filariasis, serological monitoring, elimination, Mali 4 5 Abbreviations APOC: African Programme for Onchocerciasis Control; CDTI: community-directed treatment with ivermectin; CFA: circulating filarial antigen; CMFL: community microfilarial load; ELISA: enzyme-linked immunosorbent assay; EOT: elimination of transmission; EPHP: elimination Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa318/5811165 by guest on 29 April 2020 as a public health problem; FMPOS: Faculty of Medicine, Pharmacy and Odontostomatology; FTS: filariasis test strip; GPELF: Global Programme to Eliminate Lymphatic Filariasis; ICT: immunochromatographic card test; IgG4: immunoglobulin G4; LF: lymphatic filariasis; MDA: mass drug administration; mf: microfilarial; mff: microfilariae; OCP: Onchocerciasis Control Programme in West Africa; PCR: polymerase chain reaction; RDT: rapid diagnostic test; spp: species; ss: skin snip; TAS: transmission assessment survey; USTTB: University of Sciences, Techniques and Technologies of Bamako; WHO: World Health Organization; 95% CI: ninety five percent confidence interval. 5 6 Onchocerciasis and lymphatic filariasis (LF) are endemic in Mali [1] but large-scale interventions have progressed towards elimination of transmission (EOT) for onchocerciasis and elimination as a public health problem (EPHP) for LF. The Onchocerciasis Control Programme in West Africa (OCP) began vector control in Mali in 1977, identifying and larviciding Simulium (blackfly) breeding sites [2]. Some endemic parts of Mali were included Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa318/5811165 by guest on 29 April 2020 in the OCP western extension, with ivermectin mass drug administration (MDA) starting in 1987. MDA was initially delivered by mobile teams and later by community-directed treatment with ivermectin (CDTI) assisted by the African Programme for Onchocerciasis Control (APOC) [3]. The Global Programme to Eliminate Lymphatic Filariasis (GPELF) started in Mali in 2004, supporting ivermectin and albendazole distribution [1]. In 2010, APOC launched a conceptual and operational framework for onchocerciasis elimination with ivermectin treatment [4], spurred by promising findings in foci of Mali and Senegal using this strategy. In 2012, following the World Health Organization (WHO) roadmap on neglected tropical diseases [5], the target for onchocerciasis changed from morbidity control to EOT, contrasting with the LF goal of EPHP [6]. Mali became one of the first African countries to demonstrate the principle of onchocerciasis elimination by ivermectin MDA as the sole intervention when elimination was documented in the Bakoye and Falémé foci, in 2009 and 2012 [7,8], following 15 (Bakoye) and 16 (Falémé) years of annual treatment. Treatment duration corresponds to first–last year when all first- line villages were treated, 1992–2006 (Bakoye) and 1991–2006 (Falémé) [7]. Because the LF programme started in 2007 in the same river basins, ivermectin distribution continued de facto for 9 years after 2006 (LF MDA stopped in 2016), bringing treatment duration to 24–25 years. Since 2011, a bednet distribution programme for malaria (which would also impact Anopheles-transmitted LF [9], the type occurring in Mali) was implemented. For onchocerciasis, a threshold of <0.1% seropositivity (by IgG4 ELISA) to the Onchocerca volvulus Ov16 antigen in children aged <10 years is currently recommended by the WHO for 6 7 stopping ivermectin MDA [10]. For Anopheles-transmitted LF, the WHO guidelines recommend a threshold of <2% seropositivity to Wuchereria bancrofti circulating filarial antigen (CFA) with the filariasis test strip (FTS) (which replaced the immunochromatographic card test, ICT) in 6–7-year olds before ivermectin plus albendazole MDA may be stopped [11]. Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciaa318/5811165 by guest on 29 April 2020 LF transmission assessment surveys (TAS) were conducted in 2016 and treatment stopped because all the health districts of the two foci passed the TAS using FTS, i.e. W. bancrofti antigenemia prevalence after 9 years of treatment was <2% at health district level [12], where sampling followed a community-based (household) design according to the WHO TAS protocol [11]. Documenting onchocerciasis elimination in Bakoye and Falémé was based on skin snip microscopy for detection and quantification of O. volvulus microfilaridermia, and PCR-based pool screening of blackfly samples for detection of infective, L3 larvae [7,8]. These data, alongside historical infection trends and treatment coverage information were later modelled using EPIONCHO and ONCHOSIM to estimate the risk of resurgence in Bakoye and the neighbouring